An Uproar about the IVC

So on the ISepsis section of the blog, Paul just posted on the uselessness of IVC ultrasound for fluid assessment. Now since I don't really believe in large volume repletion anymore, I don't really care about fluid responsiveness all that much either. But I never let a good opportunity for debate pass me by, so it was a delightful happenstance that one of the authors of a negative trial on IVC ultrasound for fluid responsiveness sent me an email a few weeks ago. It seems Dr. Keith Corl, who was lead author of a 2002 trial mentioned in Paul's post, did not let the matter go. He just published a repeated, and in his estimation, much better trial:

I'll be posting a wee about it and Paul's post very soon; EMNerd tells me he is working on one as well. In the meanwhile, why don't you read through the trial and tell us what you think in the comments section.

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This should be good… looking forward to the ensuing podcast and Rory’s post. Fluid responsiveness is an interesting surrogate, but I don’t believe that it has been proven to improve outcomes. Most of the crystalloid that we give to septic/inflamed patients will eventually end up in the tissues. Even if this fluid is able to cause a transient increase in cardiac output prior to transuding into the tissues (“fluid responsiveness”), eventually it’s still probably harming the patient. Off the top of my head I can only think of a few RCTs evaluating fluid: – FEAST (fluid boluses in African children increased mortality) – FACTT (diuresis in ARDS patients improved weaning from vent) – CLASSIC (restrictive fluid strategy after initial resus was safe, maybe improved renal outcome) – PROCESS (this is a stretch but… protocol-based standard therapy patients got less fluid over first 72 hours and tended to develop less renal failure) I can’t think of any RCTs which showed that *more* fluid was beneficial (aside from the Rivers trial, which has substantial methodologic limitations). So I agree that it’s hard to get excited about large-volume resuscitation anymore, especially for septic/inflammed patients. Particularly in the ICU, true hypovolemia is unusual aside… Read more »

We can definitely argue about whether or not fluid responsiveness is the right question – but until they’re actual randomized data on this people are going to ask the question. As it is, large volume vs not large volume resuscitation isn’t a well studied topic. Totally worth looking into, maybe one of the PETAL network trials will do this soon, would be awesome if it was well designed. I have some issues with you’re references here though: FEAST: african children, with no ICU resources, esp vents, no guidance to the resuscitation at all (which is the whole point of talking about IVC – does using IVC make you give more fluid or less fluid than an unguided approach? Great question!) Also, no real data to suggest that cerebral malaria would pathophysiologically respond similarly to gram negative bacterial sepsis. THis is hardly an apples to apples comparison FACTT – explicitly NOT in the initial phase of the resuscitation. Pathophysiologically the early phase and late phases of resuscitation you’d expect to be completely different in terms of the role of fluid right? CLASSIC: 3 issues. First is “after the initial resus” – the inclusion criteria for the study was 30ml/kg prior to… Read more »

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1 year ago

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Keith Corl

Hi all. As someone who has never posted to a medical blog before today I must say that I am both simultaneously flattered and surprised that our manuscript has stimulated a debate. I’d like to make a few statements in response to a number of comments so far. #1 I’m in 100% agreement with the statement that just because a patient is fluid responsive, that doesn’t mean you should continue to give them IVF. The question of does fluid responsiveness (aka tailored resuscitation) matter needs to be examined in a prospective RCT with hard patient oriented outcomes. #2 The most robust finding of the trial was that patients with a cIVC less than 25% had a negative LR of 0.16 for fluid responsiveness. With mounting evidence of over-resuscitation being associated with worse outcomes, we suggest that clinicians use a noncollapsible IVC as a stop sign for resuscitation. We additionally recognize that our positive LR of 4.5 for cIVC greater than =25% means among this group there is a subset of non responders. Again here we’d say you have to first ask yourself “does this patient need fluid in the first place?” before you base resuscitation on the cIVC. #3 In… Read more »

Keith: At least we have “some agreement” and that is good. The post did generate a Twitter storm; which in itself is also a good thing (although I am not a Twitter fan); if the post and Twitter result in folks critically thinking about the issues and engaging in meaningful dialogue then our Dear Friend Scott has achieved an important goal. Regards, Paul

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1 year ago

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Jordan Schooler

1. The concept of fluid responsiveness and the idea that the only benefit of fluid administration is to increase cardiac output are not evidence based, and I would even argue they are likely an oversimplification. As Marik himself points out, there is a wide range of cardiac outputs in critically ill patients, and it’s been shown that artificially increasing this with inotropes does not seem to have any benefit.

2. Having used the NICOM, which seems to be a random number generator, I am extremely skeptical of a paper using it as a gold standard.

3. Putting aside the first two points, the larger problem that few are willing to talk about: even if a patient is “fluid responsive,” and will derive hemodynamic benefit from fluid temporarily—is giving fluid necessarily the right decision?

My 2 cents worth (if its worth that much). #3 is the answer. The fact that a patient is a fluid responder does not imply that the patient will benefit from fluid. Furthermore, in the responders the hemodynamic benefit is usually very small and short lived (in the septic patient); the net result is minimal hemodynamic benefit with severe tissue edema. A very important point that is often neglected is: “what’s wrong with the patient and where do you want the fluid to go.” The approach to a patient with DKA (or severe diarrhoea) and sepsis (the very patients included in the 2nd Corl study) ARE VERY different. Patients with DKA are truly dehydrated with decreased intravascular volume as well as decreased the extra-vascular, extra-cellular fluid (interstitial fluid). Crystalloids will appropriately partition into both compartments and appropriately “resuscitate” both compartments. Patients with severe sepsis/septic shock are typically not dehydrated; they suffer from veno- and vasodilatation with a RELATIVE decrease in the intravascular compartment with a degree of tissue edema. Crystalloids may make the vasodilation worse and WILL ALWAYS MAKE the interstitial edema catastrophically worse. It’s somewhat fascinating that Corl et al published a study in 2012 in which they concluded… Read more »

” The fact that a patient is a fluid responder does not imply that the patient will benefit from fluid.” – Totally agree. Would love to see this studied, with a randomized controlled trial of size adequate to give us meaningful data.
The reality is, that hasn’t happened. so w’re left debating physiology. I love physiology. Believe me, I make it a point to teach residents physiology all the time, it’s the basis of how we should think about medicine and pretest probabilities of therapies.Physiology is the best possible starting point for us to launch our journeys into science.

But… in the absence of empiric data to validate it, physiology remains a fairy tale.

How many large RCTs have shown us that therapies that seem based in wonderful physiology and work wonders in animal models and observational studies just don’t work in practice. Steroids for head injury anyone?

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1 year ago

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Jordan Schooler

There’s also a distinct possibility that Marik is physiologically correct about IVC ultrasound and yet operationally wrong. Maybe IVC ultrasound is a random number generator, just as I think the NICOM device is. But a random number generator will tell you not to give fluid half the time, while most physicians treating sick patients always think more fluid is the answer. So maybe even a worthless test is indeed better than our “judgement” here.

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1 year ago

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M. Ignacio Monge García

Dear Prof. Theyyyunni,
Physiology is a fact, how to use or interpret it is the matter of discussion.

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1 year ago

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Jordan Schooler

Unfortunately, physiology is not a fact. It’s a collection of hypotheses based on experimental data, attempting to simplify the behavior of an extremely complex system. When we attempt to create therapies based on physiologic reasoning, we find that they are usually ineffective, suggesting that our understanding of physiology was inadequate to begin with.

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1 year ago

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M. Ignacio Monge García

Very nice explanation and I fully agree with it. This makes even more complex the connection between the physiological phenomenon and how we interpret and use this in our therapies. As you mentioned, very often our inadequate understanding of physiology is the main problem with ineffective therapies based on “normalizing” physiological end-points. Just take as an example, CVP in hemodynamic resuscitaiton, the central oxygen saturation, or supranormal DO2 in septic patients. I think we cannot say that ” in the absence of empiric data to validate it, physiology remains a fairy tale”, as Dr Theyyyunni suggested in his comment.

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1 year ago

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Matthew McClure

The problem with both CVP and cIVC is that they do a poor job of reflecting vascular capacitance unless that capacitance is at an extreme (high/low). This, I think is the black box of all of this. If we figure where on the pressure volume curve the capacitance of the vascular system lies we can better understand the IVCs or CVPs ability to reflect a response to a fluid bolus. Im curious if this could be quantified by calculating the IVC changes in response to fluid bolus i.e. as the volume change begins to drop with subsequent boluses then capacitance approaches a fixed variable and CVP and cIVC can more reliably reflect actual physiological state. As an aside, I asked this of Marik in his CVP post but I’m curious of peoples thoughts about using serum Osmo as a surrogate for reflecting volume status better than CVP or cIVC. It seems to me that it would better reflect a driver of the flux in capacitance at least? Thoughts? am I way out in left field?

The main utility of IVC US in my practice is around fluid safety. We use a nearly completely non-invasive system to monitor (some art lines). IVC gives some data – which needs to be interpreted in the specific context of the individual patient. A flat / near 100% collapsed IVC is probably useful to know about? However, if giving vasopressors achieves the same “plumping” of the IVC as a gallon of fluid – then I don’t need to know if they are “fluid responsive”. To me a flat ivc just means something needs doing. The “what” depends on the other data we have about this particular patient… are they bleeding, are they a cholera victim or are the septic with pneumonia- all need different strategies On the other side a full / unmoving IVC is tougher to call. There are soooo many other causes. Once again, look at the patient- but I would not hang much on it as a marker of volume state. So why do we need a neat “cut off” of collapsibility? 25 % looks great in the paper above ( lots of caveats ). I think I’d prefer to err on the side of specificity here… Read more »

More Reflections. I believe that the study by Cori et al is fatally flawed primarily as the patient population consisted of patients with sepsis (44%) COMBINED with those with DKA/HHS (38%). These are two clearly distinct disorders and from a fluid management perspective are managed completely differently. The management of DKA/HHS is not controversial with well-established universally accepted treatment guidelines. [1] Conversely, the fluid treatment strategy in patients with sepsis is more controversial with no universally recognized approach. The primary inclusion criteria for this study was “acute circulatory failure”. Having treated patients with DKA/HHS for over 30 years in both a resource poor and resource unlimited setting, acute circulatory failure is distinctly uncommon in patients with DKA/HHS. These patients are dehydrated, acute circulatory failure (shock) will only occur due to a complicating condition such as massive AMI or sepsis. Acidosis (a criterion for circulatory failure in this study) is almost never primarily due to circulatory failure in patients with DKA/HHS. It is therefore likely that the majority of patients with DKA/HHS enrolled with this study did not have acute circulatory failure (shock) and were likely inappropriately managed (from a fluid perspective). References 1. Kitabchi AE, Umpierrez GE, Miles JM et… Read more »